The objective of the proposed research is to detect morphological changes that occur at the level of the cell surface in the course of carcinogenesis and tumor evolution. An attempt will be made to relate these changes to the growth behavior of endocrine tumors. Experimentally induced mammary tumors of the rat and ovarian tumors of the mouse have been selected for examination. Some incipient mammary and granulosa cell tumors are hormone dependent and therefore provide a means of producing growth or regression by simple hormonal manipulations. Repeated serial transplantation into highly inbred hosts will be used to hasten the production of hormone independent and metastatic tumors. These different forms of tumor growth will be the basis of a comparative study centered on the intercellular junctions and other surface properties of tumor cells. Special attention will be given to gap junctions (nexus junctions). These junctions increase in frequency under the influence of certain hormones and decrease in frequency in the course of carcinogenesis. It is of special interest therefore to investigate the fate of nexus junctions in endocrine tumors in various stages of growth and evolution. Specimens will be prepared for electron microscopy using the following techniques: 1) standard thin sectioning including use of extracellular tracers, 2) special procedures for preserving and enhancing contrast of cell coats in thin sections and 3) freeze-cleave replication for detailed examination of the internal aspects of cell membranes.